Chenchen Sun, Xueqian Qian, Yahui Lu, Yi Yuan, Hui Zhang, Lanning Bai, Min Cheng, Yangyang Han
School of Life Science and Technology, Shandong Second Medical University, Weifang, 261053, Shandong, People's Republic of China.
School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, 261053, Shandong, People's Republic of China.
Mol Cell Biochem. 2025 Jan;480(1):607-620. doi: 10.1007/s11010-024-04991-5. Epub 2024 Apr 16.
The treatment of ovarian cancer remains a medical challenge and its malignant progression is connected with obvious changes in both tissue and cell stiffness. However, the accurate mechanical-responsive molecules and mechanism remains unclear in ovarian cancer. Based on our previous results combined with the crucial regulatory role of STAT3 in the malignant progression of various cancer types, we want to investigate the relationship between STAT3 and matrix stiffness in ovarian cancer and further explore the potential mechanisms. Collagen-coated polyacrylamide gels (1, 6, and 60 kPa) were prepared to mimic soft or hard matrix stiffness. Western blotting, qRT-PCR, flow cytometry, IHC, EdU assays, and TEM were used to evaluate the effect of STAT3 in vitro under different matrix stiffnesses. Furthermore, a BALB/c nude mouse model was established to assess the relationship in vivo. Our results confirmed the differential expression of STAT3/p-STAT3 not only in normal and malignant ovarian tissues but also under different matrix stiffnesses. Furthermore, we verified that STAT3 was a mechanically responsive gene both in vitro and in vivo, and the mechanical response was carried out by altering the migration-related molecules (TNFAIP1) and adhesion-related molecules (LPXN, CNN3). The novel findings suggest that STAT3, a potential therapeutic target for clinical diagnosis and treatment, is a mechanically responsive gene that responds to matrix stiffness, particularly regulation in migration and adhesion in the progression of ovarian cancer.
卵巢癌的治疗仍然是一项医学挑战，其恶性进展与组织和细胞硬度的明显变化有关。然而，卵巢癌中精确的机械反应分子和机制仍不清楚。基于我们之前的研究结果，并结合STAT3在各种癌症类型恶性进展中的关键调节作用，我们想要研究卵巢癌中STAT3与基质硬度之间的关系，并进一步探索潜在机制。制备了胶原蛋白包被的聚丙烯酰胺凝胶（1、6和60 kPa）以模拟软或硬的基质硬度。采用蛋白质免疫印迹法、定量逆转录聚合酶链反应、流式细胞术、免疫组织化学、EdU检测和透射电子显微镜来评估不同基质硬度下STAT3在体外的作用。此外，建立了BALB/c裸鼠模型来评估体内的关系。我们的结果证实了STAT3/p-STAT3不仅在正常和恶性卵巢组织中，而且在不同基质硬度下均有差异表达。此外，我们证实STAT3在体外和体内都是一种机械反应基因，并且这种机械反应是通过改变迁移相关分子（TNFAIP1）和黏附相关分子（LPXN、CNN3）来实现的。这些新发现表明，STAT3作为临床诊断和治疗的潜在靶点，是一种对基质硬度有反应的机械反应基因，特别是在卵巢癌进展过程中对迁移和黏附的调节。
